Results from the phase 3 SELECT-MONOTHERAPY clinical trial were announced.
This ongoing study evaluated Upadacitinib ( ABT-494 ), an investigational oral JAK1-selective inhibitor, as a monotherapy treatment in patients with moderate to severe rheumatoid arthritis who did not adequately respond to treatment with Methotrexate.
Results showed that after 14 weeks of treatment, both once-daily doses of Upadacitinib ( 15 mg and 30 mg ) met the study's primary endpoints of ACR20 and low disease activity ( LDA ) versus continuing prior stable methotrexate therapy.
Both doses also achieved all ranked and all key secondary endpoints.
Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.
Rheumatoid arthritis, which affects an estimated 23.7 million people worldwide, is a chronic and debilitating disease.
Methotrexate is commonly used as a first-line therapy in rheumatoid arthritis, but many patients do not respond to or cannot tolerate Methotrexate, which puts them at risk for disease progression.
This trial addresses the clinical impact of switching from Methotrexate to Upadacitinib as monotherapy in patients with an inadequate response to Methotrexate.
Results suggested that both doses of Upadacitinib can provide clinically meaningful responses.
The study showed that at week 14, 68/42/23% of patients switched to 15 mg once-daily Upadacitinib and 71/52/33% of patients switched to 30 mg once-daily Upadacitinib achieved an ACR20/50/70 response, compared to 41/15/3% of patients continuing on Methotrexate.
These results were statistically significant ( p less than 0.001 for all comparisons ) compared to patients who continued on their baseline Methotrexate dose.
Additionally, a significantly higher proportion of Upadacitinib patients in both dose groups achieved LDA and clinical remission targets at week 14 compared to patients continuing on Methotrexate ( p less than 0.001 ).
Low disease activity was achieved by 45% and 53% of patients in the 15 mg and 30 mg groups, respectively, compared to 19% of patients continuing on Methotrexate.
Clinical remission was achieved by 28% and 41% of patients in the 15 mg and 30 mg groups, respectively, compared to 8% of patients continuing on Methotrexate.
In this study, the safety profile of Upadacitinib was consistent with previously reported phase 3 SELECT clinical trials and phase 2 studies.
No new safety signals were detected.
Serious adverse events occurred in 5/3% of patients in the 15 mg/30 mg Upadacitinib groups, respectively, compared to 3% in the Methotrexate group.
One patient, with pre-existing cardiovascular risk factors, had a fatal event of hemorrhagic stroke caused by a ruptured aneurysm, while receiving Upadacitinib 15 mg.
There was one event of pulmonary embolism in the study, which occurred in the 15 mg dose group in a patient with pre-existing risk factors for pulmonary embolism.
Across the SELECT rheumatoid arthritis program, including both the placebo-controlled and extension periods, the rate of deep vein thrombosis and pulmonary embolism remains consistent with the background rate for the patient population with rheumatoid arthritis. ( Xagena )
Source: Abbvie, 2017